We will explore how baseline Brain Age delta moderates longitudinal PACC through a linear mixed effects model on four cohorts: - A4/LEARN - HABS - ADNI CU - ADNI MCI
Plot individual PACC trajectories with spaghetti plot.
Simplest Quadratic mixed effects models with delta interaction:
PACC ~ time_mri^2 + time_mriXdelta + Cumulative_Dose_Scaled + LMSTORY + time_mriXcohort
## Delta effect: -0.13 [ -0.16 , -0.11 ] p-val: 2.4e-31
## Linear vs Quadratic p-value: 2.103132e-225
## Placebo estimated coefficient: -0.1551076
## Using placebo data p-value: 4.106173e-15
Amyloid is not included because cohort already takes this into account as LEARN are those that are ab- compared to A4 which are ab+. This leads to singularity back solve if ab_status included.
Add Age, APOE, Sex, Education:
## Adding demographics estimated coefficient: -0.1338491
## Adding demographcis p-value: 3.591945e-27
Changing the model’s outcome to be change from baseline PACC and adding baseline PACC as covariate as well as the other covariates.
## Change from baseline estimated coefficient: -0.108671
## Change from baseline p-value: 8.000335e-22
## BrainAge delta * AB effect: -0.08 [ -0.1 , -0.06 ] p-val: 9.1e-15
## BrainAge delta effect: -0.1152364 p-val 0.2389577
## AB-PET effect: -0.1711032 p-val 7.876463e-26
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.07723652
## Adding gemographcis p-value: 7.175197e-14
Keeping only participants with Aβ-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.07599732
## Participants within 1 year p-value: 1.316486e-13
## BrainAge delta * pTau217 effect: -0.082 [ -0.12 , -0.043 ] p-val: 3.7e-05
## BrainAge delta effect: -0.1385027 p-val 0.6917959
## pTau217 effect: -0.1516978 p-val 1.948391e-09
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.08280586
## Adding gemographcis p-value: 2.820792e-05
Keeping only participants with ptau217 within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.08249384
## Participants within 1 year p-value: 2.839139e-05
## BrainAge delta * tau217 effect: -0.04 [ -0.074 , -0.0066 ] p-val: 0.019
## BrainAge delta effect: -0.07947587 p-val 0.1136393
## Tau-PET effect: -0.2666492 p-val 6.617619e-29
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.04179501
## Adding gemographcis p-value: 0.01552705
Keeping only participants with Tau-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.04066546
## Participants within 1 year p-value: 0.01678838
Plot individual PACC trajectories with spaghetti plot.
Simplest Quadratic mixed effects models with delta interaction:
PACC ~ time_mri^2 + time_mriXdelta
## Delta effect: -0.19 [ -0.25 , -0.12 ] p-val: 2e-08
## Linear vs Quadratic p-value: 1.135385e-29
Add Age, AB_status, APOE, Sex, Education:
## Adding demographics estimated coefficient: -0.1619889
## Adding gemographcis p-value: 2.151955e-08
Changing the model’s outcome to be change from baseline PACC and adding baseline PACC as covariate as well as the other covariates.
## Change from baseline estimated coefficient: -0.1298601
## Change from baseline p-value: 8.483627e-07
## BrainAge delta * AB effect: -0.14 [ -0.19 , -0.09 ] p-val: 7.7e-08
## BrainAge delta effect: -0.1238888 p-val 0.692033
## AB-PET effect: -0.2553744 p-val 1.284431e-18
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.1431507
## Adding gemographcis p-value: 1.729151e-08
Keeping only participants with Aβ-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.1424051
## Participants within 1 year p-value: 1.672194e-08
## BrainAge delta * pTau217 effect: -0.1 [ -0.15 , -0.051 ] p-val: 7.9e-05
## BrainAge delta effect: -0.1137161 p-val 0.8075654
## pTau217 effect: -0.2524029 p-val 1.239013e-15
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.09989929
## Adding gemographcis p-value: 6.028792e-05
Keeping only participants with pTau217 within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.09607232
## Participants within 1 year p-value: 0.0001538245
## BrainAge delta * Tau-PET effect: -0.16 [ -0.21 , -0.11 ] p-val: 2.1e-10
## BrainAge delta effect: -0.08404526 p-val 8.317191e-09
## Tau-PET effect: -0.266444 p-val 3.759346e-22
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.1523043
## Adding gemographcis p-value: 1.318138e-09
Keeping only participants with Tau-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.09506168
## Participants within 1 year p-value: 0.002124821
Plot individual PACC trajectories with spaghetti plot.
Simplest Quadratic mixed effects models with delta interaction:
PACC ~ time_mri^2 + time_mriXdelta
## Delta effect: -0.06 [ -0.14 , 0.018 ] p-val: 0.13
## Linear vs Quadratic p-value: 1.604416e-34
Add Age, AB_status, APOE, Sex, Education:
## Adding demographics estimated coefficient: -0.07607362
## Adding gemographcis p-value: 0.04307728
Changing the model’s outcome to be change from baseline PACC and adding baseline PACC as covariate as well as the other covariates.
## Change from baseline estimated coefficient: -0.0687274
## Change from baseline p-value: 0.2274667
## BrainAge delta * AB effect: -0.082 [ -0.14 , -0.023 ] p-val: 0.0066
## BrainAge delta effect: -0.04730671 p-val 0.9729352
## AB-PET effect: -0.2511428 p-val 2.244352e-12
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.09089808
## Adding gemographcis p-value: 0.002281148
Keeping only participants with Aβ-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.07689109
## Participants within 1 year p-value: 0.06353713
## BrainAge delta * pTau217 effect: -0.031 [ -0.17 , 0.11 ] p-val: 0.66
## BrainAge delta effect: -0.1491414 p-val 0.266085
## pTau217 effect: -0.3237629 p-val 2.979294e-06
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.04223502
## Adding gemographcis p-value: 0.542991
Keeping only participants with pTau217 within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: 0.3156053
## Participants within 1 year p-value: 0.1161702
## BrainAge delta * tau217 effect: 0.02 [ -0.12 , 0.16 ] p-val: 0.78
## BrainAge delta effect: -0.05364147 p-val 0.67397
## Tau-PET effect: -0.3393406 p-val 5.18895e-08
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: 0.0299743
## Adding gemographcis p-value: 0.6701048
Keeping only participants with Tau-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: 0.09882073
## Participants within 1 year p-value: 0.09062627
Plot individual PACC trajectories with spaghetti plot.
Simplest Quadratic mixed effects models with delta interaction:
PACC ~ time_mri^2 + time_mriXdelta
## Delta effect: -0.31 [ -0.39 , -0.24 ] p-val: 4.1e-16
## Linear vs Quadratic p-value: 1.203515e-17
Add Age, AB_status, APOE, Sex, Education:
## Adding demographics estimated coefficient: -0.28556
## Adding gemographcis p-value: 1.084173e-14
Changing the model’s outcome to be change from baseline PACC and adding baseline PACC as covariate as well as the other covariates.
## Change from baseline estimated coefficient: -0.3015663
## Change from baseline p-value: 7.848485e-09
## BrainAge delta * AB effect: -0.11 [ -0.17 , -0.036 ] p-val: 0.0031
## BrainAge delta effect: -0.2031691 p-val 0.01174901
## AB-PET effect: -0.3317746 p-val 7.104952e-13
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.1145484
## Adding gemographcis p-value: 0.001296245
Keeping only participants with Aβ-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.132618
## Participants within 1 year p-value: 0.0001834934
## BrainAge delta * pTau217 effect: -0.26 [ -0.43 , -0.094 ] p-val: 0.0027
## BrainAge delta effect: -0.1015306 p-val 0.1195543
## pTau217 effect: -0.2858083 p-val 0.01438463
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.2837596
## Adding gemographcis p-value: 0.003975296
Keeping only participants with pTau217 within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.1594625
## Participants within 1 year p-value: 0.4318319
## BrainAge delta * tau217 effect: -0.18 [ -0.4 , 0.035 ] p-val: 0.1
## BrainAge delta effect: -0.07658245 p-val 0.1871747
## Tau-PET effect: -0.3496441 p-val 0.00505171
Adding Age, Sex, Education, E4 Status as covariates
## Adding demographics estimated coefficient: -0.1788944
## Adding gemographcis p-value: 0.1531457
Keeping only participants with Tau-PET within 1 year of MRI.
## Adding demographics and only particiapnts within 1 year of MRI estimated coefficient: -0.01118535
## Participants within 1 year p-value: 0.9067547
Forest plots to summarize all the information of linear mixed effects models
## All Cohorts BrainAge delta effect: -0.17 [ -0.34 , -0.006 ] p-val: 0.046
## CU Cohorts BrainAge delta effect: -0.13 [ -0.21 , -0.057 ] p-val: 0.018
## All Cohorts BrainAge AB-PET effect: -0.092 [ -0.13 , -0.051 ] p-val: 0.0055
## CU Cohorts BrainAge AB-PET effect: -0.088 [ -0.15 , -0.027 ] p-val: 0.025
## All Cohorts BrainAge pTau217 effect: -0.091 [ -0.15 , -0.03 ] p-val: 0.018
## CU Cohorts BrainAge pTau217 effect: -0.086 [ -0.13 , -0.041 ] p-val: 0.014
## All Cohorts BrainAge Tau-PET effect: -0.086 [ -0.22 , 0.05 ] p-val: 0.14
## CU Cohorts BrainAge Tau-PET effect: -0.076 [ -0.29 , 0.14 ] p-val: 0.27
Run all linear mixed effects models from exploratory analysis with all subjects available.
## All Cohorts BrainAge pTau217 effect: -0.091 [ -0.13 , -0.056 ] p-val: 0.0039
## CU Cohorts BrainAge pTau217 effect: -0.091 [ -0.15 , -0.032 ] p-val: 0.022
## All Cohorts BrainAge tau effect: -0.045 [ -0.18 , 0.093 ] p-val: 0.38
## CU Cohorts BrainAge tau effect: -0.076 [ -0.26 , 0.11 ] p-val: 0.22